N-benzyloxy-2-hydroxybenzamide | 932380-41-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-benzyloxy-2-hydroxybenzamide
• 英文别名: 2-hydroxy-N-phenylmethoxybenzamide
• CAS: 932380-41-1
• 化学式: C₁₄H₁₃NO₃
• mdl: MFCD15748947
• 分子量: 243.262
• InChiKey: ULRXCHCXZMEYQM-UHFFFAOYSA-N

物化性质

• 熔点：
  106-108 °C
• 密度：
  1.245±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-benzyloxy-2-hydroxybenzamide 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以64%的产率得到水杨基羟肟酸
  参考文献：
  名称：

  Inhibitors of the FEZ-1 metallo-β-lactamase

  摘要：

  Metallo-beta-lactamases (MBLs) catalyze the hydrolysis of beta-lactams including penicillins, cephalosporins and carbapenems. Starting from benzohydroxamic acid (1) structure-activity studies led to the identification of selective inhibitors of the FEZ-1 MBL, e.g., 2,5-substituted benzophenone hydroxamic acid 17 has a K-i of 6.1 +/- 0.71 mu M against the FEZ-1 MBL but does not significantly inhibit the IMP-1, Bell, CphA or L1 MBLs. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.11.053
• 作为产物：
  描述：

  N-(benzyloxy)-2-[(2-methoxyethoxy)methoxy]benzamide 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以74%的产率得到N-benzyloxy-2-hydroxybenzamide
  参考文献：
  名称：

  Inhibitors of the FEZ-1 metallo-β-lactamase

  摘要：

  Metallo-beta-lactamases (MBLs) catalyze the hydrolysis of beta-lactams including penicillins, cephalosporins and carbapenems. Starting from benzohydroxamic acid (1) structure-activity studies led to the identification of selective inhibitors of the FEZ-1 MBL, e.g., 2,5-substituted benzophenone hydroxamic acid 17 has a K-i of 6.1 +/- 0.71 mu M against the FEZ-1 MBL but does not significantly inhibit the IMP-1, Bell, CphA or L1 MBLs. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.11.053

文献信息

• Formation and HERON Reactivity of Cyclic N,N-Dialkoxyamides
  作者：Stephen A. Glover、Adam A. Rosser、Avat (Arman) Taherpour、Ben W. Greatrex

  DOI：10.1071/ch13557

  日期：——

  Cyclic N,N-dialkoxyamides have been made, for the first time, by hypervalent iodine oxidation of β- and γ-hydroxyhydroxamic esters 17, 19, and 21. The fused γ-lactam products, N-butoxy- and N-benzyloxybenzisoxazolones (22a and 22b), are stable while alicyclic γ-lactam and δ-lactam products, 24 and 25, although observable by NMR spectroscopy and ESI-MS are unstable at room temperature, undergoing HERON reactions. The γ-lactam 24 undergoes exclusive ring opening to give a butyl ester-functionalised alkoxynitrene 28. The δ-lactam 25, instead, undergoes a HERON ring contraction to give butyrolactone (27). The structures of model γ- and δ-lactams 6, 7, and 8 have been determined at the B3LYP/6-31G(d) level of theory and the γ-lactams are much more twisted than the acyclic N,N-dimethoxyacetamide (5) resulting in a computed amidicity for 6 of only 25 % that of N,N-dimethylacetamide (3). The HERON reactions of N,N-dimethoxyacetamide (5) and alicyclic models 6 and 8 have been modelled computationally. The facile ring opening of 6 (EA = 113 kJ mol–1) and ring contraction of 8 (EA = 145 kJ mol–1) are predicted well, when compared with the HERON rearrangement of 5 (EA = 178 kJ mol–1).

  通过对 β- 和 γ- 羟基羟肟酯 17、19 和 21 进行高价碘氧化，首次制得了环状 N,N-二烷氧基酰胺。融合的 γ-内酰胺产物、N-丁氧基和 N-苄氧基苯并异恶唑酮（22a 和 22b）是稳定的，而脂环 γ-内酰胺和 δ-内酰胺产物 24 和 25 虽然可以通过核磁共振光谱和 ESI-MS 观察到，但在室温下不稳定，会发生 HERON 反应。γ-内酰胺 24 发生排他性开环，生成丁酯官能化的烷氧基腈 28。而 δ-内酰胺 25 则发生 HERON 缩环反应，生成丁内酯（27）。在 B3LYP/6-31G(d)理论水平上确定了模型γ-内酰胺和δ-内酰胺 6、7 和 8 的结构，γ-内酰胺比无环状的 N,N-二甲氧基乙酰胺（5）扭曲得多，因此 6 的计算酰胺度仅为 N,N-二甲基乙酰胺（3）的 25%。对 N,N-二甲氧基乙酰胺（5）与脂环模型 6 和 8 的 HERON 反应进行了模拟计算。与 5 的 HERON 重排反应（EA = 178 kJ mol-1）相比，6 的简易开环反应（EA = 113 kJ mol-1）和 8 的缩环反应（EA = 145 kJ mol-1）预测结果良好。
• Hydroxamic Acids as PARP‐1 Inhibitors: Molecular Design and Anticancer Activity of Novel Phenanthridinones
  作者：Denys Bondar、Olga Bragina、Ji Young Lee、Ivan Semenyuta、Ivar Järving、Volodymyr Brovarets、Peter Wipf、Ivet Bahar、Yevgen Karpichev

  DOI：10.1002/hlca.202300133

  日期：2023.10

  Poly(ADP-ribose)polymerase-1 (PARP-1) is a promising target for antitumor agents. This study presents the first evidence of hydroxamic acids as efficient PARP inhibitors. Molecular docking and molecular dynamics simulations revealed that N−O substituted phenanthridinones form a complex interplay with PARP-1. A series of cyclic aryl hydroxamic acids, N-(benzyloxy)- and N-(hydroxy)phenanthridinones,

  聚（ADP-核糖）聚合酶-1 (PARP-1) 是抗肿瘤药物的一个有前景的靶标。这项研究首次证明异羟肟酸是有效的 PARP 抑制剂。分子对接和分子动力学模拟表明，N -O 取代的菲啶酮与 PARP-1 形成复杂的相互作用。一系列环状芳基异羟肟酸、N- (苄氧基)-和N- (羟基)菲啶酮是通过无配体方法从N- (苄氧基)苯甲酰胺使用双CH/N-H键活化制备的。三种计算出的命中化合物在基于细胞和酶的测定中表现出显着的活性，在低纳摩尔范围内抑制 PARP-1。在癌细胞（HepG2、BxPC3、MDA-MD-231 和 HeLa）和非癌细胞系（NIH 3T3 和 HEK 293）中评估了所有制备的化合物以及参考化合物 PJ34 和 OlaPARib 的抗增殖活性。N- (苄氧基)-和N- (羟基)菲啶酮显示出最有前景的特性，可作为开发亚微摩尔活性窗口疗法的先导化合物。该研究强调了这种支架对于 PARP
• Palladium-Catalyzed Heteroannulation of Salicylamides with Propargyl Carbonates: Synthesis of 1,4-Benzoxazepin-5-ones
  作者：Masahiro Abe、Megumu Kawamoto、Akiho Mizukami、Tetsutaro Kimachi、Kiyofumi Inamoto

  DOI：10.1021/acs.joc.4c00898

  日期：2024.7.19

  Herein, we report a palladium-catalyzed method to synthesize 1,4-benzoxazepin-5-ones using salicylamides and propargyl carbonates. The heteroannulation provides a wide range of products in good to excellent yields with broad functional group tolerance. In addition, H2O is used as a low-cost, abundant, and safe solvent, which is important in terms of sustainability.

  在此，我们报道了一种使用水杨酰胺和碳酸炔丙酯合成 1,4-苯并氮杂卓-5-酮的钯催化方法。杂环化提供了多种产品，产率良好至优异，并且具有广泛的官能团耐受性。此外，H 2 O被用作低成本、丰富且安全的溶剂，这对于可持续性而言很重要。
• Facile entry into structurally diverse, privileged, (hetero)arene-fused N-alkoxy 3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-ones
  作者：Alexander Sapegin、Elena Reutskaya、Alexey Smirnov、Mikhail Korsakov、Mikhail Krasavin

  DOI：10.1016/j.tetlet.2016.11.064

  日期：2016.12

  Rare and highly medicinally relevant N-alkoxy-substituted benzo[1,4]oxazepines have been synthesized conveniently via the base-promoted SNAr/Smiles rearrangement/SNAr tandem cyclization of N-alkoxysalicylamides with a range of bis-electrophilic substrates; subsequent de-alkylation gives rise to the respective N-hydroxy versions. The compounds reported herein significantly add to the contemporary arsenal of small molecule tools for drug discovery. (C) 2016 Elsevier Ltd. All rights reserved.